Lithocholic acid-based oligomers as drug delivery candidates targeting model of lipid raft.

This study presents a new approach to designing a lithocholic acid functionalized oligomer (OLithocholicAA-X) that can be used as a drug carrier with additional, beneficial activity. Namely, this novel oligomer can incorporate an anti-cancer drug due to the application of an effective backbone as its component (lithocholic acid) alone is known to have anticancer activity. The oligomer was synthesized and characterized in detail by nuclear magnetic resonance, attenuated total reflectance Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, thermal analysis, and mass spectrometry analysis. We selected lipid rafts as potential drug carrier-membrane binding sites. In this respect, we investigated the effects of OLithocholicAA-X on model lipid raft of normal and altered composition, containing an increased amount of cholesterol (Chol) or sphingomyelin (SM), using Langmuir monolayers and liposomes. The surface topography of the studied monolayers was additionally investigated by atomic force microscopy (AFM). The obtained results showed that the investigated oligomer has affinity for a system that mimics a normal lipid raft (SM:Chol 2:1). On the other hand, for systems with an excess of SM or Chol, thermodynamically unfavorable fluidization of the films occurs. Moreover, AFM topographies showed that the amount of SM determines the bioavailability of the oligomer, causing fragmentation of its lattice.

The Equilibria of Triterpene Sapogenins-Phosphatidylcholine in Monolayers at the Air/Water Interface.

Sapogenins are the non-sugar parts of saponins (aglycones), high-molecular-weight glycosides linked to one or more sugar side chains. This group of compounds presents many properties, e.g., the potent properties of reducing surface tension and foaming properties, as evidenced by the amphipathic nature of these substances. They are used in the cosmetics industry, the washing and detergent industry, and the food industry. In addition, they have many healing properties. They lower blood cholesterol but are also used to synthesize steroid drugs or hormones. As reported in the literature, saponins also show antitumor activity, leading to cell cycle inhibition and apoptosis of various neoplastic cells. In this study, the influence of two sapogenins: asiatic acid (AA) and oleanolic acid (OA), on the properties of monolayers made of phosphatidylcholine (DPPC) was investigated. The method used in these studies was the Langmuir method with Brewster angle microscopy. The interactions between the tested compounds in mixed monolayers were described. Using mathematical equations, we established that oleanolic acid and asiatic acid formed complexes with DPPC at 1:1 ratios, characterized by high stability constants. We derived the parameters characterizing the formed complexes and described the phase transitions that occur during the formation of pure and mixed monolayers.

Site of the Hydroxyl Group Determines the Surface Behavior of Bipolar Chain-Oxidized Cholesterol Derivatives─Langmuir Monolayer Studies Supplemented with Theoretical Calculations.

Cholesterol oxidation products (called oxysterols) are involved in many biological processes, showing both negative (e.g., neurodegenerative) and positive (e.g., antiviral and antimicrobial) effects. The physiological activity of oxysterols is undoubtedly closely related to their structure (i.e., the type and location of the additional polar group in the cholesterol skeleton). In this paper, we focus on determining how a seemingly minor structural change (introduction of a hydroxyl moiety at C(24), C(25), or C(27) in the isooctyl chain of cholesterol) affects the organization of the resulting molecules at the phase boundary. In our research, we supplemented the classic Langmuir monolayer technique, based on the surface pressure and electric surface potential isotherms, with microscopic (BAM) and spectroscopic (PM-IRRAS) techniques, as well as theoretical calculations (DFT and MD). This allowed us to show that 24-OH behaves more like cholesterol and forms stable, rigid monolayers. On the other hand, 27-OH, similar to 25-OH, undergoes the phase transition from monolayer to bilayer structures. Theoretical calculations enabled us to conclude that the formation of bilayers from 27-OH or 25-OH is possible due to the hydrogen bonding between adjacent oxysterol molecules. This observation may help to understand the factors responsible for the unique biological activity (including antiviral and antimicrobial) of 27-OH and 25-OH compared to other oxysterols.

The Effect of Selected Flavonoids and Lipoic Acid on Natural and Model Cell Membranes: Langmuir and Microelectrophoretic Methods.

The influence of kaempferol (K), myricetin (M) and lipoic acid (LA) on the properties of natural erythrocytes, isolated from animal blood and biological membrane models (monolayers and liposomes) made of phosphatidylcholine (PC), cholesterol (CHOL), and sphingomyelin (SM), CHOL in a ratio of 10:9, was investigated. The Langmuir method, Brewster angle microscopy (BAM) and microelectrophoresis were used. The presented results showed that modification of liposomes with kaempferol, myricetin and lipoic acid caused changes in the surface charge density and the isoelectric point value. Comparing the tested systems, several conclusions were made. (1) The isoelectric point for the DPPC:Chol:M (~2.2) had lower pH values compared to lipoic acid (pH~2.5) and kaempferol (pH~2.6). (2) The isoelectric point for the SM-Chol with myricetin (~3.0) had lower pH values compared to kaempferol (pH~3.4) and lipoic acid (pH~4.7). (3) The surface charge density values for the DPPC:Chol:M system in the range of pH 2-9 showed values from 0.2 to -2.5 × 10-2 C m-2. Meanwhile, for the DPPC:Chol:K and DPPC:Chol:LA systems, these values were higher at pH~2 (0.7 × 10-2 C m-2 and 0.8 × 10-2 C m-2) and lower at pH~9 (-2.1 × 10-2 C m-2 and -1.8 × 10-2 C m-2), respectively. (4) The surface charge density values for the SM:Chol:M system in the range of pH 2-9 showed values from 0.5 to -2.3 × 10-2 C m-2. Meanwhile, for the DPPC:Chol:K and DPPC:Chol:LA systems, these values were higher at pH~2 (0.8 × 10-2 C m-2), and lower at pH~9 (-1.0 × 10-2 C m-2 and -1.8 × 10-2 C m-2), respectively. (5) The surface charge density values for the erythrocytes with myricetin in the range of pH 2-9 showed values from 1.0 to -1.8 × 10-2 C m-2. Meanwhile, for the erythrocytes:K and erythrocytes:LA systems, these values, at pH~2, were 1.3 × 10-2 C m-2 and 0.8 × 10-2 C m-2 and, at pH~9, -1.7 × 10-2 C m-2 and -1.0 × 10-2 C m-2, respectively.

Study of Nano h-BN Impact on Lubricating Properties of Selected Oil Mixtures.

Our experiments aimed to study the influence of layered materials with nanometric-scale particles, which are part of lubricant oils, on their tribological properties. The object of this study was a lubricant oil made using base oil PAO4, which contained nanoparticle hexagonal boron nitride (nano h-BN) and a dispersant based on succinic acid imide. Comparative tests for engine oil (CB30) were also performed. The paper presents the method of preparing the test material and the tribological test results, including wear spot diameter (wear mark), limit wear load, and seizure load. The test results obtained demonstrate that nano-hexagonal boron nitride improves the tribological properties of lubricant oils. However, oil preparation and the quantitative selection of components markedly influence the results.

Interactions between Phosphatidylcholine and Kaempferol or Myristicin: Langmuir Monolayers and Microelectrophoretic Studies.

Flavonoid compounds are known for their antibacterial, anti-inflammatory, and anticancer properties. Therefore, they can influence membrane properties that interest us, modifying both their structure and functions. We used kaempferol (K) and myricetin (M) as representatives of this group. We investigated the influence of the abovementioned compounds on model cell membranes' properties (i.e., Langmuir monolayers and liposomes). The basic research methods used in these studies were the Langmuir method with Brewster angle microscopy and microelectrophoresis. The π-A isotherms were registered for the pure components and mixtures of these compounds with phosphatidylcholine (PC) in appropriate volume ratios. Using mathematical equations, we established that kaempferol, myricetin, and the lipids formed complexes at 1:1 ratios. We derived the parameters characterizing the formed complexes, i.e., the surfaces occupied by the complexes and the stability constants of the formed complexes. Using the microelectrophoretic method, we determined the dependence of the lipid membranes' surface charge density as a function of the pH (in the range of 2 to 10) of the electrolyte solution. The presented results indicate that the PC membrane's modification with kaempferol or myricetin affected changes in the surface charge density and isoelectric point values.

25-hydroxycholesterol interacts differently with lipids of the inner and outer membrane leaflet - The Langmuir monolayer study complemented with theoretical calculations.

25-hydroxycholesterol (25-OH), a molecule with unusual behavior at the air/water interface, being anchored to the water surface alternatively with a hydroxyl group at C(3) or C(25), has been investigated in mixtures with main membrane phospholipids (phosphatidylcholines - PCs, and phosphatidylethanolamines - PEs), characteristic of the outer and inner membrane leaflet, respectively. To achieve this goal, the classical Langmuir monolayer approach based on thermodynamic analysis of interactions was conducted in addition to microscopic imaging of films (in situ with BAM and after transfer onto mica with AFM), surface-sensitive spectroscopy (PM-IRRAS), as well as theoretical calculations. Our results show that the strength of interactions is primarily determined by the kind of polar group (strong, attractive interactions leading to surface complexes formation were found to occur with PCs while weak or repulsive ones with PEs). Subsequently, the saturation of phosphatidylcholines apolar chain(s) was found to be crucial for the structure of the formed complexes. Namely, saturated PC (DPPC) does not have preferences regarding the orientation of 25-OH molecule in surface complexes (which results in the two possible 25-OH arrangements), while unsaturated PC (DOPC) enforces one specific orientation of oxysterol (with C(3)-OH group). Our findings suggest that the transport of 25-OH between inner and outer membrane leaflet can proceed without orientation changes, which is thermodynamically advantageous. This explains results found in real systems showing significant differences in the rate of transmembrane transport of 25-OH and the other chain-oxidized oxysterols compared to their ring-oxidized analogues or cholesterol.

Experimental and Theoretical Approaches to Describing Interactions in Natural Cell Membranes Occurring as a Result of Fatal Alcohol Poisoning.

We propose herein a theoretical model describing the effect of fatal ethanol poisoning on the equilibria between cell membranes and the surrounding ions. Using this model, we determined the parameters characterizing the interaction between the electrolyte solution's ions and the functional groups on the blood cells' surface. Via the application of mathematical equations, we calculated the total surface concentrations of the acidic and basic groups, cA and cB, and their association constants with solution ions, KAH and KBOH. Using the determined parameters and mathematical equations' values, we calculated the theoretical surface charge density values. We verified the proposed model by comparing these values with experimental data, which were selected based on measurements of the electrophoretic mobility of erythrocyte and thrombocyte membranes. Compatibility of the experimental and theoretical surface charge density values was observed in the range of pH 2-8, while deviations were observed at higher pH values.

How the replacement of cholesterol by 25-hydroxycholesterol affects the interactions with sphingolipids: The Langmuir Monolayer Study complemented with theoretical calculations.

In this paper, a representative of chain-oxidized sterols, 25-hydroxycholesterol (25-OH), has been studied in Langmuir monolayers mixed with the sphingolipids sphingomyelin (SM) and ganglioside (GM1) to build lipid rafts. A classical Langmuir monolayer approach based on thermodynamic analysis of interactions was complemented with microscopic visualization of films (Brewster angle microscopy), surface-sensitive spectroscopy (polarization modulation-infrared reflection-absorption spectroscopy) and theoretical calculations (density functional theory modelling and molecular dynamics simulations). Strong interactions between 25-OH and both investigated sphingolipids enabled the formation of surface complexes. As known from previous studies, 25-OH in pure monolayers can be anchored to the water surface with a hydroxyl group at either C(3) or C(25). In this study, we investigated how the presence of additional strong interactions with sphingolipids modifies the surface arrangement of 25-OH. Results have shown that, in the 25-OH/GM1 system, there are no preferences regarding the orientation of the 25-OH molecule in surface complexes and two types of complexes are formed. On the other hand, SM enforces one specific orientation of 25-OH: being anchored with the C(3)-OH group to the water. The strength of interactions between the studied sphingolipids and 25-OH versus cholesterol is similar, which indicates that cholesterol may well be replaced by oxysterol in the lipid raft system. In this way, the composition of lipid rafts can be modified, changing their rheological properties and, as a consequence, influencing their proper functioning.

Interactions between Beta-2-Glycoprotein-1 and Phospholipid Bilayer-A Molecular Dynamic Study.

This study aims to investigate the interactions appearing when the beta-2-glycoprotein-1 binds to a lipid bilayer. The inter- and intra-molecular forces acting between the two macromolecular systems have been investigated using a molecular dynamics simulation method. The importance of water bridges has also been addressed. Additionally, the viscoelastic response of the bilayer has been studied. In detail, the (saturated-chain) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and (unsaturated-chain) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) bilayers have been chosen to test their behavior near the protein. Both of the lipids have a polar head but different chemical structures and are similar to the main phospholipids present in the synovial fluid. This study is meaningful for further explaining the worsening friction properties in articular cartilage, as the inactivation of phospholipid bilayers by beta-2-glycoprotein-1 is believed to be a cause of the destruction of cartilage in most rheumatic diseases and osteoarthritis. It was found that the protein binds stronger to the DPPC bilayer than to the POPE, but in both cases, it has the potential to change the local bilayer stability. Nevertheless, the binding forces are placed within a small area (only a few lipids contribute to the binding, creating many interactions). However, together, they are not stronger than the covalent bonds between C-O, thus, potentially, it is possible to push the lipids into the bilayer but detaching the lipids' heads from the tail is not possible. Additionally, the protein causes water displacement from the vicinity of the bilayer, and this may be a contributor to the instability of the bilayer (disrupting the water bridges needed for the stabilization of the bilayer, especially in the case of DPPC where the heads are not so well stabilized by H-bonds as they are in POPE). Moreover, it was found that the diffusivity of lipids in the DPPC bilayer bound to the protein is significantly different from the diffusivity of the ones which are not in contact with the protein. The POPE bilayer is stiffer due to intramolecular interactions, which are stronger than in the DPPC; thus, the viscous to elastic effects in the POPE case are more significant than in the case of the DPPC. It is, therefore, harder to destabilize the POPE bilayer than the DPPC one.

Research on the Influence of the Manufacturing Process Conditions of Iron Sintered with the Addition of Layered Lubricating Materials on its Selected Properties.

The purpose of the conducted experiments was to test the selected properties of materials intended for porous sintered bearings containing layered materials in the form of powders with an average particle size of 0.5-1.5 µm, with very good tribological properties. The subject of the research was a sinter based on iron powder with the addition of layered materials; molybdenum disulfide MoS2 (average particle size 1.5 µm), tungsten disulfide WS2 (average particle size 0.6 µm), hexagonal boron nitride, h-BN (average particle size 0.5 and 1.5 µm) with two different porosities. The article presents the results of density and porosity tests, compressive strength, metallographic and tribological tests and the assessment of changes in the surface condition occurring during the long storage period. The use of layered additives allows for an approximately 20% lower coefficient of friction. In the case of sulfides, the technological process of pressing 250 MPa, 350 MPa, and sintering at a temperature of 1120 °C allows us to obtain a material with good strength and tribological properties, better than in the case of h-BN. However, the main problem is the appearance of elements from the decomposition of sulfide compounds in the material matrix, which results in rapid material degradation. In hexagonal boron nitride, such disintegration under these conditions does not occur; the material as observed does not degrade. In this case, the material is characterized by lower hardness, resulting from a different behavior of hexagonal boron nitride in the pressing and sintering process; in this case, pressing at a pressure of 350 MPa seems to be too low. However, taking into account that even with these technological parameters, the obtained material containing 2.5% h-BN with an average grain size of 1.5 µm allowed obtaining a coefficient of friction at the level of 0.41, which, with very good material durability, seems to be very positive news before further tests.

The Equilibria in Lipid-Lipoic Acid Systems: Monolayers, Microelectrophoretic and Interfacial Tension Studies.

In this examination, we investigated the effect of lipoic acid (LA) on the properties of biological membrane models (monolayers, bilayers, and liposomes) formed from phosphatidylcholine (PC) or phosphatidylserine (PS) using the Langmuir, microelectrophoresis, and interfacial tension methods. The Langmuir technique allowed us to calculate the π-A isotherms and determine the molecular surface areas of pure and mixed monolayers. Using mathematical equations, we established that LA and the lipids formed complexes at a 1:1 ratio. The interfacial tension method was based on Young and Laplace's equation. We assumed the formation of a 1:1 complex in the PC-LA system. Using the mathematical relationships, we derived the parameters characterizing the resulting complex, i.e., the surface occupied by the complex and the interfacial tension and stability constant of the formed complex. The microelectrophoretic method was used to determine the dependence of the zeta potential of the lipid membranes as a function of the pH (pH 2 to 10) of the electrolyte solution. The results indicate that modification of PC or PS membranes with LA affects changes in the zeta potential and the isoelectric point values.

Unusual Behavior of the Bipolar Molecule 25-Hydroxycholesterol at the Air/Water Interface-Langmuir Monolayer Approach Complemented with Theoretical Calculations.

In this study, 25-hydroxycholesterol (25-OH), a biamphiphilic compound with a wide range of biological activities, has been investigated at the air/water interface. We were interested in how two hydroxyl groups attached at distal positions of the 25-OH molecule (namely, at C(3) in the sterane system and at C(25) in the side chain) influence its surface behavior. Apart from traditional Langmuir monolayers, other complementary surface-sensitive techniques, such as electric surface potential measurements, Brewster angle microscopy (BAM, enabling texture visualization and film thickness measurements), and polarization modulation-infrared reflection-absorption spectroscopy (PM-IRRAS), were applied. Experimental data have been interpreted with the aid of theoretical study. Our results show that 25-OH molecules in the monomolecular layer are anchored to the water surface alternatively with C(3) or C(25) hydroxyl groups. Theoretical calculations revealed that the populations of these alternative orientations were not equal and molecules anchored with C(3) hydroxyl groups were found to be in excess. As a consequence of such an arrangement, surface films of 25-OH are of lower stability as compared to cholesterol (considered as a non-oxidized analogue of 25-OH). Moreover, it was found that, upon compression, the transition from mono- to bilayer occurred. The molecular mechanism and interactions stabilizing bilayer structure were proposed. The explanation of the observed unusual surface behavior of 25-OH may contribute to an understanding of differences in biological activity between chain- and ring-oxidized sterols.

Thermodynamic, viscoelastic and electrical properties of lipid membranes in the presence of astaxanthin.

Among numerous compounds found in marine organisms, astaxathin has received considerable research interest due to beneficial impact on health such as anti-inflammatory, antioxidant and neuroprotective activity. Recently new functionalities of this xanthophyll have been revealed indicating important applications in nutrition and pharmacy. However, astaxanthin, as the bioactive, has limited value without a protecting carrier that provides controlled release in a human body. Fabrication of liposomes as efficient drug delivery systems is promising strategy that may overcome these problems. However, the development of new delivery systems requires comprehensive understanding of physicochemical properties of carotenoids and their carriers as well as the interactions between them. The aim of this study was to investigate the mixed lipid-sterol monolayer in the presence of astaxanthin in terms of thermodynamic, morphological and viscoelastic behaviour. The results have been discussed in relation to pure lipid-sterol films. In addition we determined the surface charge density of the liposomes built of these components. The results are helpful in better understanding the role of interfacial viscoelasticity in the quality of liposomal drug delivery forms.

Influence of Manufacturing Technology on the Structure of 80W-20Re Heavy Sinters.

Preliminary measurement results of 80W-20Re heavy sinters are presented in this paper. Tested samples were taken from three different technology processes, i.e., resistance sintering (RS), pulse plasma sintering (PPS), and conventional sintering in a vacuum furnace. In the first two cases, the obtained sinters were of similar usable properties (porosity and microhardness), while for vacuum sintering, the material with high porosity was obtained. At the same time, it was found that sintering with the use of electric current (RS, PPS) generates microstructures with highly elongated grains.

The Amphoteric and Hydrophilic Properties of Cartilage Surface in Mammalian Joints: Interfacial Tension and Molecular Dynamics Simulation Studies.

In this paper, we explain the amphoteric character of the cartilage surface by studying a lipid bilayer model built from phospholipids. We examined the interfacial tension values and molecular dynamics simulation in solutions of varying pH. The effects of negative and positive charge density (or fixed charges) on the (cartilage/cartilage) friction coefficient were investigated. In physiological (or synovial) fluid, after the isoelectric point (pI), the curve of interfacial tension decreases rapidly as it reaches pH 7.4 and then approaches a constant value at higher pH. It was shown that the curve of the interfacial tension curve exhibits a maximum value at the isoelectric point with a Gaussian shape feature. The phospholipid bilayers facilitate an almost frictionless contact in the joint. Moreover, the slippage of the bilayer and the short-range repulsion between the surfaces of the negatively charged cartilage surfaces are the main determinants of the low frictional properties of the joint.

Complex formation equilibria between cholesterol and diosgenin analogues in monolayers determined by the Langmuir method.

The purpose of this study was to investigate the interaction between diosgenin analogues [DioA: diosgenin acetate (DAc) and (25R)-5α,6ß-dihydroxyspirostan-3ß-ol acetate (DSol)] and cholesterol (Ch) monolayers at the air/water interface. The surface tension of pure and mixed lipid monolayers at 22 °C was measured by using the Langmuir method with a Teflon trough and a Nima 9002 tensiometer. The surface tension values were used to calculate the π-A isotherms and to determine the molecular surface areas. The interactions between Ch and each DioA resulted in significant deviations from the additivity rule. The theory described in this work was used to determine the stability constants, the areas occupied by one molecule of Ch-DAc or Ch-DSol, and the complex formation energy (Gibbs free energy) values.

The effect of divalent ions on L-α-phosphatidylcholine from egg yolk monolayers at the air/water interface.

The Langmuir monolayers of L-α-phosphatidylcholine from egg yolk were studied by Wilhelmy method. The surface pressure versus molecular area isotherm of lipid on pure water and different subphase (with a presence of divalent ions: Sr2+, Cd2+, Ba2+, Pb2+) was obtained. The limiting area of the isotherms depends on the presence of subphase ions. The addition of divalent ions to the subphase stabilized the monolayers and increased the limiting areas of the monolayer. During the compression in monolayer complexes of 1:1 and 2:1 stoichiometry between L-α-phosphatidylcholine from egg yolk and divalent ions are formed. We used the equilibrium theory to describe the behavior of monolayer components at the air/water interface. An equilibrium theory to describe the behavior of monolayer components at the air/water interface was developed in order to obtain the stability constants and area occupied by one molecule of LMe2+ or L2Me2+ complexes, and complex formation energy (Gibbs free energy) values. These mathematically derived and experimentally confirmed values are of great importance for the interpretation of phenomena occurring in lipid monolayers and bilayers.

Hyaluronic acid and phospholipid interactions useful for repaired articular cartilage surfaces-a mini review toward tribological surgical adjuvants.

This mini review is focused on the emerging nexus between the medical device and pharmaceutical industries toward the treatment of damaged articular cartilage. The physical rationale of hyaluronic acid and phospholipid preparations as tribological surgical adjuvants for repaired articular cartilage surfaces is explored, with directions for possible new research which have arisen due to the therapeutic advance of the physiochemical scalpel. Because synovial joint lubrication regimes become dysfunctional at articular cartilage lesion sites as a result of the regional absence of the surface active phospholipid layer and its inability to reform without surgical repair, hyaluronic acid and phospholipid intra-articular injections have yielded inconsistent efficacy outcomes and only short-term therapeutic benefits mostly due to non-tribological effects. Parameters for hydrophobic-polar type interactions as applied to the lubricating properties of normal and osteoarthritic synovial fluid useful for repaired articular cartilage surfaces are discussed.

The Equilibria of Diosgenin-Phosphatidylcholine and Diosgenin-Cholesterol in Monolayers at the Air/Water Interface.

Diosgenin (Dio) has shown many treatment properties, but the most important property is cytotoxic activity in cancer cells. In this study, we investigated monolayers of Dio, cholesterol (Ch), and phosphatidylcholine (PC) at the air/water interface. The measurements were carried with a Langmuir Teflon trough and a Nima 9000 tensiometer program. The surface tension values of pure and mixed monolayers were used to calculate π-A isotherms and determine molecular surface areas. We were able to demonstrate the formation of complexes between Dio and PC and Dio and Ch molecules also. We considered the equilibrium between individual components and the formed complexes. In addition, we established that diosgenin and the lipids formed highly stable 1:1 complexes.